Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: Systematic review, network meta-analysis and cost-effectiveness analysis

Health Technology Assessment

Volumn 21, Issue 9, 2017, Pages 1-385

  Sterne, Jonathan A C ^a   Bodalia, Pritesh N ^b,c   Bryden, Peter A ^a   Davies, Philippa A ^a   López López, Jose A ^a   Okoli, George N ^a   Thom, Howard H Z ^a   Caldwell, Deborah M ^a   Dias, Sofia ^a   Eaton, Diane ^d   Higgins, Julian P T ^a   Hollingworth, Will ^a   Salisbury, Chris ^a   Savović, Jelena ^a   Sofat, Reecha ^e,f   Stephens Boal, Annya ^g   Welton, Nicky J ^a   Hingorani, Aroon D ^e,f  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON HOSPITALS   (United Kingdom)

^c ROYAL NATIONAL ORTHOPAEDIC HOSPITAL   (United Kingdom)

^d Anticoagulation Europe   (United Kingdom)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

^f LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^g Thrombosis UK   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; APIXABAN; ARDEPARIN; BETRIXABAN; CERTOPARIN; CLOPIDOGREL; DABIGATRAN; DABIGATRAN ETEXILATE; DALTEPARIN; EDOXABAN; ENOXAPARIN; FONDAPARINUX; LOW MOLECULAR WEIGHT HEPARIN; NADROPARIN; PLACEBO; RIVAROXABAN; TINZAPARIN; WARFARIN;

ANTICOAGULANT THERAPY; ATRIAL FIBRILLATION; BLEEDING; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; COST EFFECTIVENESS ANALYSIS; DEEP VEIN THROMBOSIS; DRUG COST; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; ECONOMIC EVALUATION; EMBOLISM; HEALTH CARE COST; HEART INFARCTION; HUMAN; LONG TERM CARE; LUNG EMBOLISM; META ANALYSIS; MORTALITY; PRIMARY PREVENTION; QUALITY ADJUSTED LIFE YEAR; REVIEW; RISK REDUCTION; SECONDARY PREVENTION; SYSTEMATIC REVIEW; THROMBOCYTOPENIA; TRANSIENT ISCHEMIC ATTACK; VENOUS THROMBOEMBOLISM; AGE DISTRIBUTION; AGED; BLOOD PRESSURE; COST BENEFIT ANALYSIS; ECONOMICS; ELECTROCARDIOGRAPHY; FEMALE; MALE; MARKOV CHAIN; MASS SCREENING; NATIONAL HEALTH SERVICE; NETWORK META-ANALYSIS; OBSERVATIONAL STUDY; PRIMARY HEALTH CARE; PROCEDURES; PULSE RATE; SENSITIVITY AND SPECIFICITY; STANDARDS; STATISTICAL MODEL; UNITED KINGDOM; VERY ELDERLY;

AGE DISTRIBUTION; AGED; AGED, 80 AND OVER; ANTICOAGULANTS; ATRIAL FIBRILLATION; BLOOD PRESSURE; COST-BENEFIT ANALYSIS; ELECTROCARDIOGRAPHY; FEMALE; HUMANS; MALE; MARKOV CHAINS; MASS SCREENING; MODELS, ECONOMETRIC; NETWORK META-ANALYSIS; OBSERVATIONAL STUDIES AS TOPIC; PRIMARY HEALTH CARE; PULSE; SECONDARY PREVENTION; SENSITIVITY AND SPECIFICITY; STATE MEDICINE; STROKE; UNITED KINGDOM; VENOUS THROMBOEMBOLISM;

EID: 85016132692     PISSN: 13665278     EISSN: 20464924     Source Type: Journal    
DOI: 10.3310/hta21090     Document Type: Review

References (245)

1. National Collaborating Centre for Chronic Conditions. Atrial Fibrillation: National Clinical Guideline for Management in Primary and Secondary Care. London: Royal College of Physicians; 2006.
2. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998;82:2-9N. http://dx.doi.org/10.1016/S0002-9149(98)00583-9
3. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999;131:492-501. http://dx.doi.org/10.7326/0003-4819-131-7-199910050-00003
4. Lee S, Shafe AC, Cowie MR. UK stroke incidence, mortality and cardiovascular risk management 1999-2008: time-trend analysis from the General Practice Research Database. BMJ Open 2011;1:e000269. http://dx.doi.org/10.1136/bmjopen-2011-000269
5. Soliman EZ, Safford MM, Muntner P, Khodneva Y, Dawood FZ, Zakai NA, et al. Atrial fibrillation and the risk of myocardial infarction. JAMA Intern Med 2014;174:107-14. http://dx.doi.org/10.1001/jamainternmed.2013.11912
6. Smolina K, Wright FL, Rayner M, Goldacre MJ. Incidence and 30-day case fatality for acute myocardial infarction in England in 2010: national-linked database study. Eur J Public Health 2012;22:848-53. http://dx.doi.org/10.1093/eurpub/ckr196
7. Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 2000;83:657-60.
8. National Clinical Guideline Centre - Acute and Chronic Conditions. Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital. London: Royal College of Physicians; 2010.
9. Connock M, Stevens C, Fry-Smith A, Jowett S, Fitzmaurice D, Moore D, Song F. Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anticoagulation therapy: a systematic review and economic modelling. Health Technol Assess 2007;11(38). http://dx.doi.org/10.3310/hta11380
10. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18820 patients. BMJ 2004;329:15-19. http://dx.doi.org/10.1136/bmj.329.7456.15
11. National Institute for Health and Clinical Excellence (NICE). Clinical Guideline 36. National Cost Impact Report to accompany ‘Atrial Fibrillation: the Management of Atrial Fibrillation’. London: NICE; 2006.
12. Garcia D, Libby E, Crowther MA. The new oral anticoagulants. Blood 2010;115:15-20. http://dx.doi.org/10.1182/blood-2009-09-241851
13. Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 2014;63:321-8. http://dx.doi.org/10.1016/j.jacc.2013.07.104
14. Centre for Reviews and Dissemination (CRD). Systematic Reviews. CRD’s Guidance for Undertaking Reviews in Health Care. 3rd edn. York: CRD, University of York; 2009.
15. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester: Wiley; 2008. http://dx.doi.org/10.1002/9780470712184
16. Assiri A, Al-Majzoub O, Kanaan AO, Donovan JL, Silva M. Mixed treatment comparison meta-analysis of aspirin, warfarin, and new anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation. Clin Ther 2013;35:967-84.e2. http://dx.doi.org/10.1016/j.clinthera.2013.05.011
17. Castellucci LA, Cameron C, Le Gal G, Rodger MA, Coyle D, Wells PS, et al. Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis. BMJ 2013;347:f5133. http://dx.doi.org/10.1136/bmj.f5133
18. Fox BD, Kahn SR, Langleben D, Eisenberg MJ, Shimony A. Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism: direct and adjusted indirect meta-analysis of randomised controlled trials. BMJ 2012;345:e7498. http://dx.doi.org/10.1136/bmj.e7498
19. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. http://dx.doi.org/10.1136/bmj.d5928
20. Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med 2004;23:3105-24. http://dx.doi.org/10.1002/sim.1875
21. Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 2005;331:897-900. http://dx.doi.org/10.1136/bmj.331.7521.897
22. Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making 2013;33:607-17. http://dx.doi.org/10.1177/0272989X12458724
23. Spiegelhalter DJ, Best NG, Carlin BP, van der Linde A. Bayesian measures of model complexity and fit. J R Statist Soc B 2002;64:583-616. http://dx.doi.org/10.1111/1467-9868.00353
24. Berkey CS, Hoaglin DC, Mosteller F, Colditz GA. A random-effects regression model for meta-analysis. Stat Med 1995;14:395-411. http://dx.doi.org/10.1002/sim.4780140406
25. Salanti G, Higgins JP, Ades AE, Ioannidis JP. Evaluation of networks of randomized trials. Stat Methods Med Res 2008;17:279-301. http://dx.doi.org/10.1177/0962280207080643
26. Song F, Altman DG, Glenny AM, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 2003;326:472-5. http://dx.doi.org/10.1136/bmj.326.7387.472
27. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Stat Med 2010;29:932-44. http://dx.doi.org/10.1002/sim.3767
28. Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU Technical Support Document 2. A Generalised Linear Modelling Framework for Pairwise and Network Meta-analysis of Randomised Controlled Trials. London: NICE; 2011.
29. The R Foundation. The R Project for Statistical Computing. URL: www.r-project.org/(accessed 12 August 2016).
30. Lunn DJ, Thomas A, Best N, Spiegelhalter DJ. WinBUGS - a Bayesian modelling framework: concepts, structure, and extensibility. Stat Comput 2000;10:325-37. http://dx.doi.org/10.1023/A:1008929526011
31. Gage BF, Cardinalli AB, Albers GW, Owens DK. Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. JAMA 1995;274:1839-45. http://dx.doi.org/10.1001/jama.1995.03530230025025
32. Lightowlers S, McGuire A. Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke. Stroke 1998;29:1827-32. http://dx.doi.org/10.1161/01.STR.29.9.1827
33. Bayer plc. Single Technology Appraisal (STA) of Rivaroxaban (Xarelto). Newbury: Bayer plc; 2011.
34. Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011;123:2562-70. http://dx.doi.org/10.1161/CIRCULATIONAHA.110.985655
35. Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med 2011;154:1-11. http://dx.doi.org/10.7326/0003-4819-154-1-201101040-00289
36. Lee S, Mullin R, Blazawski J, Coleman CI. Cost-effectiveness of apixaban compared with warfarin for stroke prevention in atrial fibrillation. PLOS ONE 2012;7:e47473. http://dx.doi.org/10.1371/journal.pone.0047473
37. Lee S, Anglade MW, Pham D, Pisacane R, Kluger J, Coleman CI. Cost-effectiveness of rivaroxaban compared to warfarin for stroke prevention in atrial fibrillation. Am J Cardiol 2012;110:845-51. http://dx.doi.org/10.1016/j.amjcard.2012.05.011
38. Harrington AR, Armstrong EP, Nolan PE, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke 2013;44:1676-81. http://dx.doi.org/10.1161/STROKEAHA.111.000402
39. Kamel H, Easton JD, Johnston SC, Kim AS. Cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in atrial fibrillation. Neurology 2012;79:1428-34. http://dx.doi.org/10.1212/WNL.0b013e31826d5fe8
40. Wells G, Coyle D, Cameron C, Steiner S, Coyle K, Kelly S, et al. Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation. Ottawa, ON: Canadian Collaborative for Drug Safety, Effectiveness and Network Meta-Analysis, 2012.
41. Wisloff T, Tove R, Gunhild H, Asmund R, Marianne K. Efficacy and Cost-effectiveness of New Oral Anticoagulants Compared to Warfarin for the Prevention of Stroke in Patients with Atrial Fibrillation. Report from Kunnskapssenteret (Norwegian Knowledge Centre for the Health Services), no. 5. Oslo: Kunnskapssenteret; 2013.
42. Kansal AR, Sorensen SV, Gani R, Robinson P, Pan F, Plumb JM, Cowie MR. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation. Heart 2012;98:573-8. http://dx.doi.org/10.1136/heartjnl-2011-300646
43. Canestaro WJ, Patrick AR, Avorn J, Ito K, Matlin OS, Brennan TA, et al. Cost-effectiveness of oral anticoagulants for treatment of atrial fibrillation. Circ Cardiovasc Qual Outcomes 2013;6:724-31. http://dx.doi.org/10.1161/CIRCOUTCOMES.113.000661
44. Nshimyumukiza L, Duplantie J, Gagnon M, Douville X, Fournier D, Lindsay C, et al. Dabigatran versus warfarin under standard or pharmacogenetic-guided management for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation: a cost/utility analysis using an analytic decision model. Thromb J 2013;11:14. http://dx.doi.org/10.1186/1477-9560-11-14
45. Krejczy M, Harenberg J, Marx S, Obermann K, Frölich L, Wehling M. Comparison of cost-effectiveness of anticoagulation with dabigatran, rivaroxaban and apixaban in patients with non-valvular atrial fibrillation across countries. J Thromb Thrombolysis 2014;37:507-23. http://dx.doi.org/10.1007/s11239-013-0989-6
46. Pink J, Lane S, Pirmohamed M, Hughes DA. Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. BMJ 2011;343:d6333. http://dx.doi.org/10.1136/bmj.d6333
47. Lip GY, Kongnakorn T, Phatak H, Kuznik A, Lanitis T, Liu LZ, et al. Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation. Clin Ther 2014;36:192-210.e20. http://dx.doi.org/10.1016/j.clinthera.2013.12.011
48. Rognoni C, Marchetti M, Quaglini S, Liberato NL. Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. Clin Drug Investig 2014;34:9-17. http://dx.doi.org/10.1007/s40261-013-0144-3
49. Limone BL, Baker WL, Mearns ES, White CM, Kluger J, Coleman CI. Common flaws exist in published cost-effectiveness models of pharmacologic stroke prevention in atrial fibrillation. J Clin Epidemiol 2014;67:1093-102. http://dx.doi.org/10.1016/j.jclinepi.2014.05.013
50. Bayer. Rivaroxaban for the Treatment of Deep Vein Thrombosis and Prevention of Recurrent Deep Vein Thrombosis and Pulmonary Embolism. 2012.
51. Bayer. Rivaroxaban for Treating Pulmonary Embolism and Preventing Recurrent Venous Thromboembolism. 2013.
52. Boehringer Ingelheim. Dabigatran Etexilate for the Prevention of Venous Thromboembolism After Hip or Knee Replacement Surgery in Adults. 2008.
53. Botteman MF, Caprini J, Stephens JM, Nadipelli V, Bell CF, Pashos CL, et al. Results of an economic model to assess the cost-effectiveness of enoxaparin, a low-molecular-weight heparin, versus warfarin for the prophylaxis of deep vein thrombosis and associated long-term complications in total hip replacement surgery in the United States. Clin Ther 2002;24:1960-86. http://dx.doi.org/10.1016/S0149-2918(02)80091-1
54. Bayer. Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults. 2009.
55. Bristol-Myers Squibb. Apixaban for the prevention of venous thromboembolism after total hip or knee replacement in adults. 2012.
56. Dranitsaris G, Stumpo C, Smith R, Bartle W. Extended dalteparin prophylaxis for venous thromboembolic events: cost-utility analysis in patients undergoing major orthopedic surgery. Am J Cardiovasc Drugs 2009;9:45-58. http://dx.doi.org/10.1007/BF03256594
57. Duran A, Sengupta N, Diamantopoulos A, Forster F, Kwong L, Lees M. Cost effectiveness of rivaroxaban versus enoxaparin for prevention of post-surgical venous thromboembolism from a U.S. payer’s perspective. Pharmacoeconomics 2012;30:87-101. http://dx.doi.org/10.2165/11599370-000000000-00000
58. Monreal M, Folkerts K, Diamantopoulos A, Imberti D, Brosa M. Cost-effectiveness impact of rivaroxaban versus new and existing prophylaxis for the prevention of venous thromboembolism after total hip or knee replacement surgery in France, Italy and Spain. Thromb Haemost 2013;110:987-94. http://dx.doi.org/10.1160/TH12-12-0919
59. Mahmoudi M, Sobieraj DM. The cost-effectiveness of oral direct factor Xa inhibitors compared with low-molecular-weight heparin for the prevention of venous thromboembolism prophylaxis in total hip or knee replacement surgery. Pharmacotherapy 2013;33:1333-40. http://dx.doi.org/10.1002/phar.1269
60. McCullagh L, Tilson L, Walsh C, Barry M. A cost-effectiveness model comparing rivaroxaban and dabigatran etexilate with enoxaparin sodium as thromboprophylaxis after total hip and total knee replacement in the Irish healthcare setting. PharmacoEconomics 2009;27:829-46. http://dx.doi.org/10.2165/11313800-000000000-00000
61. McCullagh L, Walsh C, Barry M. Value-of-information analysis to reduce decision uncertainty associated with the choice of thromboprophylaxis after total hip replacement in the Irish healthcare setting. PharmacoEconomics 2012;30:941-59. http://dx.doi.org/10.2165/11591510-000000000-00000
62. Lundkvist J, Bergqvist D, Jönsson B. Cost-effectiveness of extended prophylaxis with fondaparinux compared with low molecular weight heparin against venous thromboembolism in patients undergoing hip fracture surgery. Eur J Health Econ 2007;8:313-23. http://dx.doi.org/10.1007/s10198-006-0017-2
63. Gordois A, Posnett J, Borris L, Bossuyt P, Jönsson B, Levy E, de Pouvourville G. The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopedic surgery. J Thromb Haemost 2003;1:2167-74. http://dx.doi.org/10.1046/j.1538-7836.2003.00396.x
64. Pishko AM, Smith KJ, Ragni MV. Anticoagulation in ambulatory cancer patients with no indication for prophylactic or therapeutic anticoagulation: a cost-effectiveness analysis from a U.S. perspective. Thromb Haemost 2012;108:303-10. http://dx.doi.org/10.1160/TH12-03-0185
65. Sullivan SD, Kwong L, Nutescu E. Cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against venous thromboembolism in patients undergoing hip fracture surgery. Value Health 2006;9:68-76.
66. Zindel S, Stock S, Müller D, Stollenwerk B. A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting. BMC Health Serv Res 2012;12:192. http://dx.doi.org/10.1186/1472-6963-12-192
67. Gómez-Outes A, Terleira-Fernández AI, Suárez-Gea ML, Vargas-Castrillón E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ 2012;344:e3675. http://dx.doi.org/10.1136/bmj.e3675
68. National Institute for Health and Clinical Excellence (NICE). NICE Clinical Guideline 36. Atrial Fibrillation: The Management of Atrial Fibrillation. London: NICE; 2006.
69. National Joint Registry Editorial Board. 10th Annual Report. Hemel Hempstead: National Joint Registry for England, Wales and Northern Ireland; 2013. URL: www.njrcentre.org.uk/njrcentre/Portals/0/Documents/England/Reports/10th_annual_report/NJR%2010th%20Annual%20Report%202013%20B.pdf (accessed 4 April 2015).
70. National Institute for Health and Care Excellence (NICE). National Clinical Guideline Centre - Acute and Chronic Conditions. Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital. Methods, Evidence and Guidance. London: National Clinical Guideline Centre - Acute and Chronic Conditions; 2010. URL: www.nice.org.uk/guidance/cg92/evidence/full-guideline-243920125 (accessed 29 September 2016).
71. National Institute for Health and Care Excellence (NICE). Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital. NICE Clinical Guideline 92. London: NICE; 2010. URL: www.nice.org.uk/guidance/cg92 (accessed 12 August 2016).
72. Briggs A, Sculpher M, Claxton K. Decision Modelling for Health Economic Evaluation. Oxford: Oxford University Press; 2006.
73. National Institute for Health and Care Excellence (NICE). Guide to the Methods of Technology Appraisal 2013. London: NICE; 2013.
74. Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ 2001;10:779-87. http://dx.doi.org/10.1002/hec.635
75. Strong M BP, Thomas C, Brennan A. Sheffield Accelerated Value of Information. Release version 2.0.8 (2015-06-19); 2015 (accessed July 2015).
76. Strong M, Oakley JE, Brennan A. Estimating multiparameter partial expected value of perfect information from a probabilistic sensitivity analysis sample: a nonparametric regression approach. Med Decis Making 2014;34:311-26. http://dx.doi.org/10.1177/0272989X13505910
77. Hori M, Connolly SJ, Zhu J, Liu LS, Lau CP, Pais P, et al. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke 2013;44:1891-6. http://dx.doi.org/10.1161/STROKEAHA.113.000990
78. Naimark DM, Bott M, Krahn M. The half-cycle correction explained: two alternative pedagogical approaches. Med Decis Making 2008;28:706-12. http://dx.doi.org/10.1177/0272989X08315241
79. Ali A, Bailey C, Abdelhafiz AH. Stroke prophylaxis with warfarin or dabigatran for patients with non-valvular atrial fibrillation-cost analysis. Age Ageing 2012;41:681-4. http://dx.doi.org/10.1093/ageing/afs017
80. Office for National Statistics (ONS). ONS Consumer Price Inflation Index for Medical Services (DKC3) for 2013/14. London: ONS; 2013. URL: www.ons.gov.uk/ons/publications/re-reference-tables.html?edition=tcm%3A77-323625,%202015%20#29 (accessed 1 November 2015).
81. Department of Health (DH). NHS Reference Costs 2012-13. London: DH; 2014.
82. Ioannides-Demos LL, Makarounas-Kirchmann K, Ashton E, Stoelwinder J, McNeil JJ. Cost of myocardial infarction to the Australian community: a prospective, multicentre survey. Clin Drug Investig 2010;30:533-43. http://dx.doi.org/10.2165/11536350-000000000-00000
83. Luengo-Fernandez R, Yiin GS, Gray AM, Rothwell PM. Population-based study of acute-and long-term care costs after stroke in patients with AF. Int J Stroke 2013;8:308-14. http://dx.doi.org/10.1111/j.1747-4949.2012.00812.x
84. National Institute for Health and Clinical Excellence (NICE). Dabigatran Etexilate for the Prevention of Venous Thromboembolism After Hip or Knee Replacement Surgery in Adults. TA157. London: NICE; 2008.
85. Caprini JA, Botteman MF, Stephens JM, Nadipelli V, Ewing MM, Brandt S, et al. Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States. Value Health 2003;6:59-64. http://dx.doi.org/10.1046/j.1524-4733.2003.00204.x
86. Locadia M, Bossuyt PM, Stalmeier PF, Sprangers MA, van Dongen CJ, Middeldorp S, et al. Treatment of venous thromboembolism with vitamin K antagonists: patients’ health state valuations and treatment preferences. Thromb Haemost 2004;92:1336-41. http://dx.doi.org/10.1160/th04-02-0075
87. Berg J, Lindgren P, Nieuwlaat R, Bouin O, Crijns H. Factors determining utility measured with the EQ-5D in patients with atrial fibrillation. Qual Life Res 2010;19:381-90. http://dx.doi.org/10.1007/s11136-010-9591-y
88. Robinson A, Thomson R, Parkin D, Sudlow M, Eccles M. How patients with atrial fibrillation value different health outcomes: a standard gamble study. J Health Serv Res Policy 2001;6:92-8. http://dx.doi.org/10.1258/1355819011927288
89. Lenert L, Soetikno RM. Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis. JAMA 1997;4:49-56. http://dx.doi.org/10.1136/jamia.1997.0040049
90. Lacey EA, Walters SJ. Continuing inequality: gender and social class influences on self perceived health after a heart attack. J Epidemiol Community Health 2003;57:622-7. http://dx.doi.org/10.1136/jech.57.8.622
91. Haacke C, Althaus A, Spottke A, Siebert U, Back T, Dodel R. Long-term outcome after stroke: evaluating health-related quality of life using utility measurements. Stroke 2006;37:193-8. http://dx.doi.org/10.1161/01.STR.0000196990.69412.fb
92. Kind P, Hardman G, Macran S. UK Population Norms for EQ-5D. York: Centre for Health Economics, University of York; 1999.
93. Meads DM, McKenna SP, Doughty N, Das C, Gin-Sing W, Langley J, Pepke-Zaba J. The responsiveness and validity of the CAMPHOR Utility Index. Eur Respir J 2008;32:1513-19. http://dx.doi.org/10.1183/09031936.00069708
94. McKenna SP, Ratcliffe J, Meads DM, Brazier JE. Development and validation of a preference based measure derived from the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for use in cost utility analyses. Health Qual Life Outcomes 2008;6:65. http://dx.doi.org/10.1186/1477-7525-6-65
95. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet 1989;1:175-9. http://dx.doi.org/10.1016/S0140-6736(89)91200-2
96. Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994;343:687-91.
97. Gulløv AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J, Boysen G. Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Arch Intern Med 1998;158:1513-21. http://dx.doi.org/10.1001/archinte.158.14.1513
98. Hellemons BS, Langenberg M, Lodder J, Vermeer F, Schouten HJ, Lemmens T, et al. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. BMJ 1999;319:958-64. http://dx.doi.org/10.1136/bmj.319.7215.958
99. Hu DY, Zhang HP, Sun YH, Jiang LQ, Antithrombotic Therapy in Atrial Fibrillation Study Group. [The randomized study of efficiency and safety of antithrombotic therapy in nonvalvular atrial fibrillation: warfarin compared with aspirin.] Zhonghua Xin Xue Guan Bing Za Zhi 2006;34:295-8.
100. Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006;367:1903-12. http://dx.doi.org/10.1016/S0140-6736(06)68845-4
101. Rash A, Downes T, Portner R, Yeo WW, Morgan N, Channer KS. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007;36:151-6. http://dx.doi.org/10.1093/ageing/afl129
102. Ezekowitz MD, Reilly PA, Nehmiz G, Simmers TA, Nagarakanti R, Parcham-Azad K, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol 2007;100:1419-26. http://dx.doi.org/10.1016/j.amjcard.2007.06.034
103. Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmauricie D, Lip GY, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493-503. http://dx.doi.org/10.1016/S0140-6736(07)61233-1
104. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51. http://dx.doi.org/10.1056/NEJMoa0905561
105. Eikelboom JW, O’Donnell M, Yusuf S, Diaz R, Flaker G, Hart R, et al. Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment. Am Heart J 2010;159:348-53.e1. http://dx.doi.org/10.1016/j.ahj.2009.08.026
106. ROCKET AF Study Investigators. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: Rationale and Design of the ROCKET AF study. Am Heart J 2010;159:340-7.e1. http://dx.doi.org/10.1016/j.ahj.2009.11.025
107. Lopes RD, Alexander JH, Al-Khatib SM, Ansell J, Diaz R, Easton JD, et al. Apixaban for reduction in stroke and other Thromboembolic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J 2010;159:331-9. http://dx.doi.org/10.1016/j.ahj.2009.07.035
108. Weitz JI, Connolly SJ, Patel I, Salazar D, Rohatagi S, Mendell J, et al. Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation. Thromb Haemost 2010;104:633-41. http://dx.doi.org/10.1160/TH10-01-0066
109. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L, Randomized Evaluation of Long-Term Anticoagulation Therapy Investigators. Newly identified events in the RE-LY trial. N Engl J Med 2010;363:1875-6. http://dx.doi.org/10.1056/NEJMc1007378
110. Yamaguchi T. A Dose Response Study of Dabigatran Etexilate (BIBR 1048) in Pharmacodynamics and Safety in Patients with Non-valvular Atrial Fibrillation in Comparison to Warfarin. NCT01136408. ClinicalTrials.gov; 2010.
111. Ruff CT, Giugliano RP, Antman EM, Crugnale SE, Bocanegra T, Mercuri M, et al. Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48). Am Heart J 2010;160:635-41. http://dx.doi.org/10.1016/j.ahj.2010.06.042
112. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91. http://dx.doi.org/10.1056/NEJMoa1009638
113. Ogawa S, Shinohara Y, Kanmuri K. Safety and efficacy of the oral direct factor Xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation - The ARISTOTLE-J study. Circ J 2011;75:1852-9. http://dx.doi.org/10.1253/circj.CJ-10-1183
114. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92. http://dx.doi.org/10.1056/NEJMoa1107039
115. Chung N, Jeon HK, Lien LM, Lai WT, Tse HF, Chung WS, et al. Safety of edoxaban, an oral factor Xa inhibitor, in Asian patients with non-valvular atrial fibrillation. Thromb Haemost 2011;105:535-44. http://dx.doi.org/10.1160/TH10-07-0451
116. Hohnloser S, Yusuf S, Eikelboom J, Steg G, Atar D, Budaj A, et al. Apixaban in patients with atrial fibrillation and their risk for cardiovascular hospitalization: insights from the AVERROES trial. Eur Heart J 2011;32:671.
117. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806-17. http://dx.doi.org/10.1056/NEJMoa1007432
118. Yamashita T, Koretsune Y, Yasaka M, Inoue H, Kawai Y, Yamaguchi T, et al. Randomized, multicenter, warfarin-controlled phase II study of edoxaban in Japanese patients with non-valvular atrial fibrillation. Circ J 2012;76:1840-7. http://dx.doi.org/10.1253/circj.CJ-11-1140
119. Hohnloser SH, Hijazi Z, Thomas L, Alexander JH, Amerena J, Hanna M, et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2012;33:2821-30. http://dx.doi.org/10.1093/eurheartj/ehs274
120. Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation - the J-ROCKET AF study -. Circ J 2012;76:2104-11. http://dx.doi.org/10.1253/circj.CJ-12-0454
121. Diener HC, Eikelboom J, Connolly SJ, Joyner CD, Hart RG, Lip GY, et al. Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial. Lancet Neurol 2012;11:225-31. http://dx.doi.org/10.1016/S1474-4422(12)70017-0
122. Chen KP, Huang CX, Huang DJ, Cao KJ, Ma CS, Wang FZ, Zhang S. Anticoagulation therapy in Chinese patients with non-valvular atrial fibrillation: a prospective, multi-center, randomized, controlled study. Chin Med J 2012;125:4355-60.
123. Hankey GJ, Patel MR, Stevens SR, Becker RC, Breithardt G, Carolei A, et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol 2012;11:315-22. http://dx.doi.org/10.1016/S1474-4422(12)70042-X
124. Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB, Wallentin L, et al. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol 2012;11:503-11. http://dx.doi.org/10.1016/S1474-4422(12)70092-3
125. Flaker GC, Hohnloser S, Wojdyla D, Hylek E, Garcia D, Sullivan R, et al. Apixaban is efficacious and safe in patients with atrial fibrillation using concomitant amiodarone: an analysis from the ARISTOTLE trial. J Am Coll Cardio 2013;1:E317. http://dx.doi.org/10.1016/S0735-1097(13)60317-4
126. Al-Khatib SM, Thomas L, Wallentin L, Lopes RD, Gersh B, Garcia D, et al. Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial. Eur Heart J 2013;34:2464-71. http://dx.doi.org/10.1093/eurheartj/eht135
127. Bahit MC, Lopes RD, Wojdyla DM, Hohnloser SH, Alexander JH, Lewis BS, et al. Apixaban in patients with atrial fibrillation and prior coronary artery disease: insights from the ARISTOTLE trial. Int J Cardiol 2013;170:215-20. http://dx.doi.org/10.1016/j.ijcard.2013.10.062
128. Connolly SJ, Eikelboom J, Dorian P, Hohnloser SH, Gretler DD, Sinha U, Ezekowitz MD. Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa). Eur Heart J 2013;34:1498-505. http://dx.doi.org/10.1093/eurheartj/eht039
129. Mahaffey KW, Wojdyla D, Hankey GJ, White HD, Nessel CC, Piccini JP, et al. Clinical outcomes with rivaroxaban in patients transitioned from vitamin K antagonist therapy: a subgroup analysis of a randomized trial. Ann Intern Med 2013;158(12):861-8. [Summary for patients in Ann Intern Med 2013;158:1-28.] http://dx.doi.org/10.7326/0003-4819-158-12-201306180-00003
130. Garcia DA, Wallentin L, Lopes RD, Thomas L, Alexander JH, Hylek EM, et al. Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. Am Heart J 2013;166:549-58. http://dx.doi.org/10.1016/j.ahj.2013.05.016
131. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-104. http://dx.doi.org/10.1056/NEJMoa1310907
132. McMurray JJ, Ezekowitz JA, Lewis BS, Gersh BJ, van Diepen S, Amerena J, et al. Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial. Circ Heart Fail 2013;6:451-60. http://dx.doi.org/10.1161/CIRCHEARTFAILURE.112.000143
133. Alexander JH, Lopes RD, Thomas L, Alings M, Atar D, Aylward P, et al. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2014;35:224-32. http://dx.doi.org/10.1093/eurheartj/eht445
134. Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol 2014;63:2141-7. http://dx.doi.org/10.1016/j.jacc.2014.02.549
135. Liu X, Huang H, Yu J, Cao G, Feng L, Xu Q, et al. Warfarin compared with aspirin for older Chinese patients with stable coronary heart diseases and atrial fibrillation complications. Int J Clin Pharmacol Ther 2014;52:454-9. http://dx.doi.org/10.5414/CP201996
136. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857-67. http://dx.doi.org/10.7326/0003-4819-146-12-200706190-00007
137. Ezekowitz MD, Bridgers SL, James KE, Carliner NH, Colling CL, Gornick CC, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med 1992;327:1406-12. http://dx.doi.org/10.1056/NEJM199211123272002
138. Cairns JA. Stroke prevention in atrial fibrillation study. Final results. Circulation 1991;84:527-39. http://dx.doi.org/10.1111/j.1524-4733.2006.00085.x
139. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990;323:1505-11. http://dx.doi.org/10.1056/NEJM199011293232201
140. Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991;18:349-55. http://dx.doi.org/10.1016/0735-1097(91)90585-W
141. EAFT (European Atrial Fibrillation Trial) Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993;342:1255-62.
142. Chimowitz MI, Furlan AJ. Prevention of stroke in atrial fibrillation. N Engl J Med 1990;323:481-4. http://dx.doi.org/10.1056/NEJM199008163230712
143. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012;33:1500-10. http://dx.doi.org/10.1093/eurheartj/ehr488
144. Andersen KK, Olsen TS. Reduced poststroke mortality in patients with stroke and atrial fibrillation treated with anticoagulants: results from a Danish quality-control registry of 22,179 patients with ischemic stroke. Stroke 2007;38:259-63. http://dx.doi.org/10.1161/01.STR.0000254622.52483.03
145. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, Brindle P. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ 2008;336:1475-82. http://dx.doi.org/10.1136/bmj.39609.449676.25
146. Office for National Statistics (ONS). National Life Tables, United Kingdom: 2011-13. Stat Bull 2014.
147. Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricker BH, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006;27:949-53. http://dx.doi.org/10.1093/eurheartj/ehi825
148. Office for National Statistics (ONS). 2011 Census, Population and Household Estimates for England and Wales. Table P04 2011. London: ONS; 2012.
149. Kamel H, Johnston SC, Easton JD, Kim AS. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke 2012;43:881-3. http://dx.doi.org/10.1161/STROKEAHA.111.641027
150. Vanassche T, Lauw MN, Eikelboom JW, Healey JS, Hart RG, Alings M, et al. Risk of ischaemic stroke according to pattern of atrial fibrillation: analysis of 6563 aspirin-treated patients in ACTIVE-A and AVERROES. Eur Heart J 2015;36:281-7a. http://dx.doi.org/10.1093/eurheartj/ehu307
151. Hohnloser SH, Pajitnev D, Pogue J, Healey JS, Pfeffer MA, Yusuf S, Connolly SJ, ACTIVE W Investigators. Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy. J Am Coll Cardiol 2007;50:2156-61. http://dx.doi.org/10.1016/j.jacc.2007.07.076
152. Leclerc JR, Geerts WH, Desjardins L, Laflamme GH, L’Espérance B, Demers C, et al. Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med 1996;124:619-26. http://dx.doi.org/10.7326/0003-4819-124-7-199604010-00001
153. Francis CW, Pellegrini VD, Totterman S, Boyd AD, Marder VJ, Liebert KM, et al. Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin. J Bone Joint Surg Am 1997;79:1365-72.
154. Colwell CW, Collis DK, Paulson R, McCutchen JW, Bigler GT, Lutz S, Hardwick ME. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am 1999;81:932-40.
155. Hull RD, Pineo GF, Francis C, Bergqvist D, Fellenius C, Soderberg K, et al. Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators. Arch Intern Med 2000;160:2199-207. http://dx.doi.org/10.1001/archinte.160.14.2199
156. Fitzgerald RH Jr., Spiro TE, Trowbridge AA, Gardner JA Jr., Whitsett TL, O’Connell MB, et al. Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin. J Bone Joint Surg Am 2001;83A:900-6.
157. Turpie AG, Fisher WD, Bauer KA, Kwong LM, Irwin MW, Kälebo P, et al. BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. J Thromb Haemost 2005;3:2479-86. http://dx.doi.org/10.1111/j.1538-7836.2005.01602.x
158. Eriksson BI, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, et al. A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation 2006;114:2374-81. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.642074
159. Eriksson BI, Borris L, Dahl OE, Haas S, Huisman MV, Kakkar AK, et al. Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost 2006;4:121-8. http://dx.doi.org/10.1111/j.1538-7836.2005.01657.x
160. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007;370:949-56. http://dx.doi.org/10.1016/S0140-6736(07)61445-7
161. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007;5:2178-85. http://dx.doi.org/10.1111/j.1538-7836.2007.02748.x
162. Lassen MR, Davidson BL, Gallus A, Pineo G, Ansell J, Deitchman D. The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. J Thromb Haemost 2007;5:2368-75. http://dx.doi.org/10.1111/j.1538-7836.2007.02764.x
163. Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;358:2776-86. http://dx.doi.org/10.1056/NEJMoa076016
164. Kanan PS, Schwartsmann CR, Boschin LC, Conrad S, Silva MF. Comparative study between rivaroxaban and enoxaparin in deep venous thromboembolism prophylaxis in patients submitted to total hip arthroplasty. Rev Bras Ortop 2008;43:319-28. http://dx.doi.org/10.1590/S0102-36162008000800002
165. Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358:2765-75. http://dx.doi.org/10.1056/NEJMoa0800374
166. Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008;372:31-9. http://dx.doi.org/10.1016/S0140-6736(08)60880-6
167. Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009;24:1-9. http://dx.doi.org/10.1016/j.arth.2008.01.132
168. Turpie AG, Bauer KA, Davidson BL, Fisher WD, Gent M, Huo MH, et al. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost 2009;101:68-76.
169. Goel DP, Buckley R, deVries G, Abelseth G, Ni A, Gray R. Prophylaxis of deep-vein thrombosis in fractures below the knee: a prospective randomised controlled trial. J Bone Joint Surg Br 2009;91:388-94. http://dx.doi.org/10.1302/0301-620X.91B3.20820
170. Agnelli G, Gussoni G, Bianchini C, Verso M, Mandalà M, Cavanna L, et al. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009;10:943-9. http://dx.doi.org/10.1016/S1470-2045(09)70232-3
171. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009;361:594-604. http://dx.doi.org/10.1056/NEJMoa0810773
172. Fuji T, Fujita S, Tachibana S, Kawai Y. Randomized, double-blind, multi-dose efficacy, safety and biomarker study of the oral factor Xa inhibitor DU-176b compared with placebo for prevention of venous thromboembolism in patients after total knee arthroplasty [abstract no. 35]. Blood 2009;112(11):19.
173. Turpie AG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373:1673-80. http://dx.doi.org/10.1016/S0140-6736(09)60734-0
174. Fuji T, Wang CJ, Fujita S, Tachibana S, Kawai Y. Edoxaban in patients undergoing total hip arthroplasty: A phase IIb dose-finding study. Blood 2009;114(22).
175. Fuji T, Fuijita S, Ujihira T, Sato T. Dabigatran etexilate prevents venous thromboembolism after total knee arthroplasty in Japanese patients with a safety profile comparable to placebo. J Arthroplasty 2010;25:1267-74. http://dx.doi.org/10.1016/j.arth.2009.08.010
176. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM, ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010;363:2487-98. http://dx.doi.org/10.1056/NEJMoa1006885
177. Raskob G, Cohen AT, Eriksson BI, Puskas D, Shi M, Bocanegra T, Weitz JI. Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study. Thromb Haemost 2010;104:642-9. http://dx.doi.org/10.1160/TH10-02-0142
178. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P, ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010;375:807-15. http://dx.doi.org/10.1016/S0140-6736(09)62125-5
179. Fuji T, Fujita S, Tachibana S, Kawai Y, Koretsune Y, Yamashita T. Efficacy and safety of edoxaban versus enoxaparin for the prevention of venous thromboembolism following total hip arthroplasty: Stars J-V trial [abstract no. 3320]. Blood 2010;116(21).
180. Fuji T, Fujita S, Tachibana S, Kawai Y. A dose-ranging study evaluating the oral factor Xa inhibitor edoxaban for the prevention of venous thromboembolism in patients undergoing total knee arthroplasty. J Thromb Haemost 2010;8:2458-68. http://dx.doi.org/10.1111/j.1538-7836.2010.04021.x
181. Fujita S, Fuji T, Tachibana S, Nakamura M, Kawai Y. Safety and efficacy of edoxaban in patients undergoing hip fracture surgery. Pathophysiol Haemost Thromb 2010;37:A95.
182. Fuji T, Wang CJ, Fujita S, Tachibana S, Kawai Y, Koretsune Y, et al. Edoxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty: the STARS E-3 trial. Pathophysiol Haemost Thromb 2010;37:A20.
183. Eriksson B, Dahl OE, Kurth AA, Hantel S, Huo MH, Hermansson K, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty: the RE-NOVATE II randomised trial. Pathophysiol Haemost Thromb 2010;37:A20.
184. Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban compared with enoxaparin for the prevention of venous thromboembolism in acutely ill medical patients: MAGELLAN study methodology. Blood 2010;116(21).
185. Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF, LIFENOX Investigators. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 2011;365:2463-72. http://dx.doi.org/10.1056/NEJMoa1111288
186. Yokote R, Matsubara M, Hirasawa N, Hagio S, Ishii K, Takata C. Is routine chemical thromboprophylaxis after total hip replacement really necessary in a Japanese population? J Bone Joint Surg Br 2011;93:251-6. http://dx.doi.org/10.1302/0301-620X.93B2.25795
187. Iliopoulos E, Fotiadis E, Kravas A, Vittis F, Nenopoulos A, Ntovas T, et al. Thromboprophylaxis management in total knee arthroplasty. Osteoporos Int 2011;22:S120-1.
188. Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, Weitz JI, ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011;365:2167-77. http://dx.doi.org/10.1056/NEJMoa1110899
189. Eriksson BI, Dahl OE, Huo MH, Kurth AA, Hantel S, Hermansson K, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost 2011;105:721-9. http://dx.doi.org/10.1160/TH10-10-0679
190. Levine MN, Gu C, Liebman HA, Escalante CP, Solymoss S, Deitchman D, et al. A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer. J Thromb Haemost 2012;10:807-14. http://dx.doi.org/10.1111/j.1538-7836.2012.04693.x
191. Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013;368:513-23. http://dx.doi.org/10.1056/NEJMoa1111096
192. Zhang H, Wang D, Sun HY, Li SW, Liu L. Efficacy and safety of rivaroxaban in the prevention of deep vein thrombosis after hip arthroplasty. Chin J Tissue Eng Res 2013;17:5440-5.
193. Fuji T, Fujita S, Kawai Y, Nakamura M, Kimura T, Kiuchi Y, et al. Safety and efficacy of edoxaban in patients undergoing hip fracture surgery. Thromb Res 2014;133:1016-22. http://dx.doi.org/10.1016/j.thromres.2014.03.009
194. Eriksson BI, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, et al. Dose-escalation study of rivaroxaban (BAY 59-7939) - an oral, direct Factor Xa inhibitor - for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Res 2007;120:685-93. http://dx.doi.org/10.1016/j.thromres.2006.12.025
195. Eriksson BI, Dahl OE, Büller HR, Hettiarachchi R, Rosencher N, Bravo ML, et al. A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost 2005;3:103-11. http://dx.doi.org/10.1111/j.1538-7836.2004.01100.x
196. Heit JA, Berkowitz SD, Bona R, Cabanas V, Corson JD, Elliott CG, Lyons R. Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for the prevention of venous thromboembolism after total knee replacement surgery: a double-blind, dose-ranging study. Ardeparin Arthroplasty Study Group. Thromb Haemost 1997;77:32-8.
197. Haas SK, Freund M, Heigener D, Heilmann L, Kemkes-Matthes B, von Tempelhoff GF, et al. Low-molecular-weight heparin versus placebo for the prevention of venous thromboembolism in metastatic breast cancer or stage III/IV lung cancer. Clin Appl Thromb Hemost 2012;18:159-65. http://dx.doi.org/10.1177/1076029611433769
198. Moise AI, Dragulin E, Casabalian D, Guran C, Mincu N, Stelea G. Dabigatran etexilate Is effective and safe in patients undergoing total hip arthoplasty. Eur J Anaesthesiol 2011;28:87. http://dx.doi.org/10.1097/00003643-201106001-00277
199. Camporese G, Bernardi E, Noventa F. Efficacy of rivaroxaban for prevention of venous thromboembolism after knee arthroscopy: a randomized double-blind trial (Erika study). J Thromb Haemost 2011;9:156-7.
200. van der Veen L, van Raay JJ, Gerritsma-Bleeker CL, Veeger NJ, van Hulst M. Direct treatment comparison of DAbigatran and RIvaroxaban versus NAdroparin in the prevention of venous thromboembolism after total knee arthroplasty surgery: design of a randomised pilot study (DARINA). BMJ Open 2013;3:e002218. http://dx.doi.org/10.1136/bmjopen-2012-002218
201. Cohen AT, Harrington R, Goldhaber SZ, Hull R, Gibson CM, Hernandez AF, et al. The design and rationale for the Acute Medically Ill Venous Thromboembolism Prevention with Extended Duration Betrixaban (APEX) study. Am Heart J 2014;167:335-41. http://dx.doi.org/10.1016/j.ahj.2013.11.006
202. Agnelli G, Gallus A, Goldhaber SZ, Haas S, Huisman MV, Hull RD, et al. Treatment of proximal deep-vein thrombosis with the oral direct factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in Patients With Acute Symptomatic Deep-Vein Thrombosis) study. Circulation 2007;116:180-7. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.668020
203. Büller HR, Lensing AW, Prins MH, Agnelli G, Cohen A, Gallus AS, et al. A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study. Blood 2008;112:2242-7. http://dx.doi.org/10.1182/blood-2008-05-160143
204. Büller H, Deitchman D, Prins M, Segers A, Botticelli Investigators, Writing Committee. Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis. The Botticelli DVT dose-ranging study. J Thromb Haemost 2008;6:1313-18. http://dx.doi.org/10.1111/j.1538-7836.2008.03054.x
205. Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009;361:2342-52. http://dx.doi.org/10.1056/NEJMoa0906598
206. Bauersachs R, Berkowitz SD, Brenner B, Büller HR, Decousus H, Gallus AS, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510. http://dx.doi.org/10.1056/NEJMoa1007903
207. Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97. http://dx.doi.org/10.1056/NEJMoa1113572
208. Raskob GE, Büller H, Angchaisuksiri P, Oh Boda Z, Lyons RM, et al. Edoxaban for long-term treatment of venous thromboembolism in cancer patients. Blood 2013;122(21).
209. Hokusai-VTE Investigators: Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013;369:1406-15. http://dx.doi.org/10.1056/NEJMoa1306638
210. Agnelli G, Büller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013;369:799-808. http://dx.doi.org/10.1056/NEJMoa1302507
211. Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H, Mismetti P, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014;129:764-72. http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004450
212. Young A, Dunn J, Chapman O, Grumett J, Marshall A, Phillips A, et al. SELECT-D: Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. J Clin Oncol 2014;32:5S.
213. Kearon C, Gent M, Hirsh J, Weitz J, Kovacs MJ, Anderson DR, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;340:901-7. http://dx.doi.org/10.1056/NEJM199903253401201
214. Agnelli G, Prandoni P, Santamaria MG, Bagatella P, Iorio A, Bazzan M, et al. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med 2001;345:165-9. http://dx.doi.org/10.1056/NEJM200107193450302
215. Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, et al. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003;139:19-25. http://dx.doi.org/10.7326/0003-4819-139-1-200307010-00008
216. Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003;348:1425-34. http://dx.doi.org/10.1056/NEJMoa035029
217. Büller HR. Once-daily oral rivaroxaban versus placebo in the long-term prevention of recurrent symptomatic venous thromboembolism. The EINSTEIN-extension study. Blood 2009;114:22.
218. Romualdi E, Donadini MP, Ageno W. Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study). Expert Rev Cardiovasc Ther 2011;9:841-4. http://dx.doi.org/10.1586/erc.11.62
219. Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012;366:1959-67. http://dx.doi.org/10.1056/NEJMoa1114238
220. Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012;367:1979-87. http://dx.doi.org/10.1056/NEJMoa1210384
221. Agnelli G, Büller HR, Cohen A, Curto M, Gallus AS, Johnson M, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013;368:699-708. http://dx.doi.org/10.1056/NEJMoa1207541
222. Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013;368:709-18. http://dx.doi.org/10.1056/NEJMoa1113697
223. Tullett J, Murray E, Nichols L, Holder R, Lester W, Rose P, et al. Trial Protocol: a randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study). BMC Cardiovasc Disord 2013;13:16. http://dx.doi.org/10.1186/1471-2261-13-16
224. Mazilu L, Parepa IR, Suceveanu AI, Suceveanu A, Baz R, Catrinoiu D. Venous thromboembolism: secondary prevention with dabigatran vs. acenocumarolin patients with paraneoplastic deep vein thrombosis. Results from a small prospective study in Romania. Cardiovasc Res 2014;103:S39. http://dx.doi.org/10.1093/cvr/cvu082.154
225. White HD. Editorial: do we need another bleeding definition? What does the Bleeding Academic Research Consortium definition have to offer? Curr Opin Cardiol 2011;26:275-8. http://dx.doi.org/10.1097/HCO.0b013e32834706a9
226. Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke 2012;43:1511-17. http://dx.doi.org/10.1161/STROKEAHA.112.650614
227. Prandoni P, Villalta S, Bagatella P, Rossi L, Marchiori A, Piccioli A, et al. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica 1997;82:423-8.
228. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007;92:199-205. http://dx.doi.org/10.3324/haematol.10516
229. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004;350:2257-64. http://dx.doi.org/10.1056/NEJMoa032274
230. Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr 1974;19:716-23. http://dx.doi.org/10.1109/TAC.1974.1100705
231. Fenwick E, Byford S. A guide to cost-effectiveness acceptability curves. Br J Psychiatry 2005;187:106-8. http://dx.doi.org/10.1192/bjp.187.2.106
232. Hamidi V, Ringerike T, Hagen G, Reikvam A, Klemp M. New anticoagulants as thromboprophylaxis after total hip or knee replacement. Int J Technol Assess Health Care 2013;29:234-43. http://dx.doi.org/10.1017/S0266462313000251
233. Lefebvre P, Coleman CI, Bookhart BK, Wang ST, Mody SH, Tran KN, et al. Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism. J Med Econ 2014;17:52-64. http://dx.doi.org/10.3111/13696998.2013.858634
234. Liew A, Eikelboom JW, O’Donnell M, Hart RG. Assessment of anticoagulation intensity and management of bleeding with old and new oral anticoagulants. Can J Cardiol 2013;29(Suppl 7):34-44. http://dx.doi.org/10.1016/j.cjca.2013.04.013
235. Yang E. A clinician’s perspective: novel oral anticoagulants to reduce the risk of stroke in nonvalvular atrial fibrillation - full speed ahead or proceed with caution? Vasc Health Risk Manag 2014;10:507-22. http://dx.doi.org/10.2147/VHRM.S68117
236. Fenger-Eriksen C, Münster AM, Grove EL. New oral anticoagulants: clinical indications, monitoring and treatment of acute bleeding complications. Acta Anaesthesiol Scand 2014;58:651-9. http://dx.doi.org/10.1111/aas.12319
237. UKMi New Drugs Online Database. New Drugs Online Report for Ciraparantag. URL: www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=6443 (accessed 18 May 2015).
238. Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014;371:2141-2. http://dx.doi.org/10.1056/NEJMc1411800
239. Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013;19:446-51. http://dx.doi.org/10.1038/nm.3102
240. UKMi New Drugs Online Database. New Drugs Online Report for Andexanet Alfa. URL: www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=6169 (accessed 18 May 2015).
241. Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, et al. A specific antidote for dabigatran: functional and structural characterization. Blood 2013;121:3554-62. http://dx.doi.org/10.1182/blood-2012-11-468207
242. UKMi New Drugs Online Database. New Drugs Online Report for Idarucizumab. URL: www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=6275 (accessed 18 May 2015).
243. Framingham Heart Study. Boston, MA. URL: www.framinghamstudy.org (accessed 22 August 2016).
244. Sorensen SV, Dewilde S, Singer DE, Goldhaber SZ, Monz BU, Plumb JM. Cost-effectiveness of warfarin: trial versus “real-world” stroke prevention in atrial fibrillation. Am Heart J 2009;157:1064-73. http://dx.doi.org/10.1016/j.ahj.2009.03.022
245. Roskell NS, Lip GY, Noack H, Clemens A, Plumb JM. Treatments for stroke prevention in atrial fibrillation: a network meta-analysis and indirect comparisons versus dabigatran etexilate. Thromb Haemost 2010;104:1106-15. http://dx.doi.org/10.1160/TH10-10-0642